Objective: To explore the effect of local chemotherapy with methotrexate via Ommaya reservoir in the treatment of malignant glioma after surgical resection. Methods: A retrospective study was conducted on 60 patients with high-grade malignant glioma in Ganzhou People’ s Hospital from January 2013 to January 2017. According to different chemotherapy methods, the above patients were divided into local chemotherapy group (n=31, methotrexate local chemotherapy via Ommaya reservoir) and conventional systemic chemotherapy group (n=29, methotrexate systemic chemotherapy). The neurological function [National Institutes of Health Stroke Scale (NIHSS)], living ability [Activity of Daily Living Scale (ADL)] and cognitive function before surgery and after chemotherapy, occurrence of toxic and side effects of chemotherapy drugs and recurrence status were compared between both groups. Results: After chemotherapy, compared with the conventional systemic chemotherapy group, the NIHSS score in the local chemotherapy group was lower while the ADL score was higher (P<0.05). The scores of dimensions of cognitive function in the local chemotherapy group after chemotherapy were higher than those in the conventional systemic chemotherapy group (P<0.05). The total incidence rate of toxic and side effects of chemotherapy drugs was lower in the local chemotherapy group than that in the conventional systemic chemotherapy group (P<0.05). The 1-year recurrence rate in the local chemotherapy group was lower and the recurrence time was longer compared to the conventional systemic chemotherapy group (P<0.05). Conclusion: Local chemotherapy with methotrexate via Ommaya reservoir after surgical resection can improve the living ability, neurological and cognitive functions of patients, reduce the occurrence of toxic and side effects of chemotherapy drugs, and lower the recurrence rate.